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PubMed1999

Dietary oat lipids-induced novel DNA modifications and suppression of altered hepatic foci formation.

Previous studies have shown that the presence of several hepatic I-compounds, i.e., age-dependent covalent DNA modifications, is related to the presence of a natural ingredient, i.e., oats, in the diet. To demonstrate the biological significance of these novel DNA modifications, the effect of oat lipids on tumor initiation and promotion was examined in a rat liver tumor model. Female Sprague-Dawley rats were treated with a single dose of diethylnitrosamine, a hepatic carcinogen, 24 hours after a 70% partial hepatectomy, then subjected to dietary phenobarbital promotion. Diets containing 10% oat lipids or corn oil were given during the initiation or the promotion stage of the tumorigenesis. At the end of the feeding, hepatic I-compounds were measured by 32P postlabeling, and the number and volume of enzyme-altered hepatic foci, which served as preneoplastic markers, were measured in serial sections of liver by the method of quantitative stereology. Rats receiving oat lipids-supplemented diets had five- to sixfold higher levels of I-compounds in their liver DNA than those receiving control diets. Meanwhile, rats receiving diets containing oat lipids during promotion had significantly smaller numbers and reduced volume of altered hepatic foci compared with those fed the control diet containing corn oil. These observations support the hypothesis that some I-compounds, e.g., the oats-specific I-compounds, are novel DNA modifications related to nutrient metabolism. The diet containing oat lipids may have chemopreventive activities, as demonstrated in this model system.

Analysis of Variance↗
PubMed2003

Anti-inflammatory properties of lipid oxidation products.

Oxidative modification of lipids occurs during inflammatory processes and leads to the formation and accumulation of biologically active lipid oxidation products that induce specific cellular reactions. These reactions lead to a modulation of the inflammatory process and may determine the fate and outcome of the body's reaction in acute inflammation during host defense. The processes by which oxidized lipids may play an important role include resolution of inflammation involving apoptosis, chronic inflammatory processes, and innate and adaptive immune responses. The classical view of lipid oxidation products is that they can induce and propagate chronic inflammatory reactions. However, evidence is accumulating that cells and tissues respond towards these oxidatively formed stress signals also by activation of anti-inflammatory processes. These include defense strategies such as (a) induction of signaling pathways leading to the upregulation of anti-inflammatory genes, (b) inhibition of signaling pathways coupled to the expression of proinflammatory genes, and (c) preventing the interaction of proinflammatory bacterial products with host cells. This contribution summarizes recent findings on the anti-inflammatory action of oxidized lipoproteins and lipid oxidation products. We discuss confirmed and suggested mechanisms as well as the (patho)physiological significance of these findings.

Animals↗
PubMedDate not supplied

Effect of a comprehensive yoga-based lifestyle modification program on lipid peroxidation.

Oxidative stress contributes to the process of aging as well as a variety of chronic degenerative diseases. There are indications that psychological stress increases oxidative stress whereas relaxation decreases it. We have measured the concentration of thiobarbituric acid reactive substances (TBARS) in blood as an indicator of oxidative stress at the beginning and at the end of a comprehensive yoga-based lifestyle modification program (YLMP). The data was collected from 104 subjects (59 male, 45 female), 19-71 years of age (mean +/- SD, 41.2 +/- 14.6 years). The YLMP consisted of a nine-day educational out-patient course on the theory and practice of yoga and included, besides a daily one-hour practice of physical postures (asanas) and breathing exercises (pranayama), lecture and films on yoga, stress management and nutrition, practice of meditation and shavasana (a relaxation technique), and individual counseling. Venous blood samples were collected on the first and last day of the course. The serum concentration of TBARS decreased significantly from 1.72 +/- 0.72 nmoles/ml on day 1 to 1.57 +/- 0.72 nmoles/ml on day 10 (P<0.05). The study suggests that a brief low cost lifestyle intervention based on yoga reduces oxidative stress.

Adult↗
PubMed2003

Maillard reaction-like lysine modification by a lipid peroxidation product: immunochemical detection of protein-bound 2-hydroxyheptanal in vivo.

2-Hydroxyheptanal (2-HH) is one of the reactive aldehyde species generated during the peroxidation of n-6 polyunsaturated fatty acids, such as linoleic and arachidonic acids. Analogous to the Maillard reaction of reducing sugars, 2-HH readily reacts with lysine epsilon-amino groups. In the present study, to define the occurrence of the Maillard reaction-like lysine modification by 2-HH in vivo, we raised a monoclonal antibody directed to a trihydropyridinone (THPO) structure, 1-alkyl-4-butyl-5-pentyl-1,2,6-trihydropyridin-3-one, formed from 2-HH and lysine, and examined the presence of the antigenic structure in the human atherosclerotic aorta. Mice were immunized with the 2-HH-modified keyhole limpet hemocyanin (KLH) as the immunogen. Using a THPO-carrier protein conjugate, we screened the hybridomas and finally obtained a clone that produced the monoclonal antibody 3C8 (mAb3C8). The antibody strongly recognized bovine serum albumin (BSA) treated with 2-HH, but showed no cross-reactivity with BSAs modified with other related aldehydes. By using this antibody, it was revealed that the antigenic structure was indeed present in atherosclerotic lesions of the human aorta.

Aldehydes↗
PubMed1997

Interaction of the 14-residue peptaibols, harzianins HC, with lipid bilayers: permeability modifications and conductance properties.

Harzianins HC are a series of 14-residue peptaibols containing three Aib-Pro motives separated by sequences of two usual amino acids (Aib-Pro-Xaa-Xaa)n. They are organized in a subtype of the 3(10)-helix, which results in an approximate length of about 27-30 A for the helical rods, allowing them to span a bilayer. Permeabilization of small unilamellar vesicles composed of zwitterionic lipids (egg phosphatidylcholine/cholesterol 7/3 and 8/2) by harzianins HC was observed as well as voltage-gated macroscopic conductance and single-channel formation in planar lipid bilayers (DOPE/POPC 7/3) The permeabilization process was shown to increase with increasing the helix global hydrophobicity. The ion channel-for ming properties appeared rather favoured by an increase in the peptide amphipathicity. The set of conductance levels increasing in geometrical progression, reflecting the sequential uptake and release of monomers which is characteristic of the barrel-stave model for ion-channels described for alamethicin was not observed. The passage of ions through the bilayer would rather be the result of a set of aggregates with fixed numbers of monomers formed in the bilayer. The permeability process and the voltage-gated properties could thus result from different mechanisms showing that harzianins HC can permeabilize membranes via bilayer destabilization or channels, depending on the membrane system, composition and application of voltage.

Amino Acid Sequence↗
PubMed1990

Effects of membrane lipid and fluidity modifications on HIV-1 infectibility of primate lymphocytes in vitro.

Although most non-human primates, except the chimpanzee and the gibbon in vivo are not infectible by HIV-1, lymphocytes of several of these species can be infected by HIV-1 in vitro. In order to investigate whether the in vitro infectibility of primate lymphocytes might be attributed to plasma membrane adaptation processes or to serum factors, we compared HIV-1 infectibility of cultivated peripheral blood lymphocytes of macaques and of baboons on day one and on day ten of cultivation. These data were correlated to plasma membrane lipid composition and membrane fluidity. We found a correlation between increased HIV-1 in vitro infectibility and changes in plasma membrane lipid composition resulting in decreased membrane fluidity of cultured primate lymphocytes.

Animals↗
PubMed2002

Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure.

OBJECTIVE: We previously demonstrated the beneficial effects of dietary flavonoids derived from the ethanolic extract of licorice root against atherosclerotic lesion development in association with inhibition of low-density lipoprotein (LDL) oxidation in atherosclerotic mice. Administration of licorice extract to normolipidemic subjects also inhibited LDL oxidation. In the present study, we extended our investigation to analyze the antiatherogenic effects of licorice-root extract consumption in moderately hypercholesterolemic patients. METHODS: Supplementation of licorice root extract (0.1 g/d) to patients for 1 mo was followed by an additional 1 mo of placebo consumption. RESULTS: Licorice consumption 1) reduced patients' plasma susceptibility to oxidation (by 19%); 2) increased resistance of plasma LDL against three major atherogenic modifications: oxidation (by 55%), aggregation (by 28%), and retention, estimated as chondroitin sulfate binding ability (by 25%); 3) reduced plasma cholesterol levels (by 5%), which was due to a 9% reduction in plasma LDL cholesterol levels; and 4) reduced (by 14%) plasma triacylglycerol levels. After the 1 mo of placebo consumption, these parameters reversed toward baseline levels. Licorice extract supplementation also reduced systolic blood pressure by 10%, which was sustained during the placebo consumption. CONCLUSIONS: Dietary consumption of licorice-root extract by hypercholesterolemic patients may act as a moderate hypocholesterolemic nutrient and a potent antioxidant agent and, hence against cardiovascular disease.

Anticholesteremic Agents↗
PubMed1986

Effects of dietary fat modifications on serum lipids and blood pressure in children.

Some recent studies have shown an extremely high level of serum cholesterol level among Finnish children. The aim of the present study was to test the effect of a "cholesterol lowering diet" on serum lipids and blood pressure among 36 children aged 8-18 years residing in two semirural communities in North Karelia, Finland. After a baseline period of two weeks on conventional diets, the proportion of energy derived from fat in the diet was reduced from the baseline level of 35% to 24%, and the ratio of polyunsaturated/saturated fats was increased from the baseline level of 0.18 to 0.61, during a 12-week intervention period. The children then changed back to their normal diet during a five-week switch-back period. The mean serum total cholesterol decreased 15% during the intervention, and then increased to nearly the initial level during the switch-back period. Similar changes were observed in HDL-cholesterol and also to some extent in apoproteins AI, AII and B. Blood pressure was not affected, although systolic blood pressure decreased during intervention. We conclude that the high level of serum cholesterol in Finnish children is to a great extent caused by the local dietary pattern and can be decreased by dietary modification.

Adolescent↗
PubMed1988

Therapeutic modification of membrane lipid abnormalities in juvenile neuronal ceroid-lipofuscinosis (Batten disease).

Five patients with juvenile neuronal ceroid-lipofuscinosis, who were shown to have absent or reduced serum prebetalipoprotein and a deficiency of polyunsaturated fatty acids in erythrocyte membrane lipids, were treated for a period of one year with supplements of fish oil extract (rich in omega-3 fatty acids) and encouraged to increase dietary intake of corn oil lipid (rich in omega-6 fatty acids) in an attempt to promote incorporation of these fatty acids into membranes. After one year there was a significant increase in omega-3 fatty acids (P less than 0.05) and in the total polyunsaturated fatty acids (P less than 0.02) in erythrocyte membranes but no change in the incorporation of omega-6 fatty acids. The patients were assessed clinically, psychometrically and neurophysiologically before and after the supplementation. No significant changes were noted after one year of treatment.

Adolescent↗
PubMed1978

Binding of protein chemotactic factors to the surfaces of neutrophil leukocytes and its modification with lipid-specific bacterial toxins.

The binding to neutrophil leukoyctes of human serum albumin (HSA), which is chemokinetic for leukocytes, i.e. influences their rate of locomotion, and of alkali-denatured HSA, which is chemotactic for leukocytes, i.e. influences their direction of locomotion, was studied. Native serum albumin showed low affinity binding to the neutrophil surface. Denatured serum albumin showed saturable binding with a Ka of approximately 1-(6) litres per mole to about 10(6) binding sites per cell. Another protein chemotactic factor, alpha5-casein, gave similar binding. These results exclude that chemotactic reactions to denatured proteins are mediated in a completely non-specific manner and suggest the presence on the cell of a restricted number of defined recognition sites. Binding was reduced following treatment of the cells with either of two lipid-specific bacterial toxins, perfringolysin, the theta-toxin of Clostridium perfringens, an oxygen-labile cholesterol-specific toxin, and Staphylococcus aureus Sphingomyelinase C. Both have previously been shown to reduce chemotactic reactions and both were used at doses which did not reduce cell viability. These results suggest an important, and possiblly direct, role for membrane lipid in the binding sites for chemotactic factors. Visual analysis of the behaviour of perfringolysin-treated neutrophils showed that these cells were still capable of chemotactic locomotion. The cells appeared to be less efficient than normal in detecting chemotactic gradients only when at a distance from the gradient source, a finding which is consistent with reduced binding of the chemotactic factor to the cell surface.

Bacterial Toxins↗
PubMed1992

Lindane-induced modifications to membrane lipid structure: effect on membrane fluidity after subchronic treatment.

Chronic lindane intoxication by injecting subcutaneously the toxicant, resulted in an altered lipid pattern in rat ventral prostate membranes. An increase of membrane fluidity was also observed using a fluorescence polarization technique. When in vitro experiments were carried out with both treated and untreated rats, an interesting lack of parallelism was found, which could indicate the development of a resistance to membrane disordering by lindane. The observed changes in cholesterol and phospholipid composition are also consistent with the hypothesis that lindane perturbs the lipid matrix of membranes, possibly inducing complex compensatory changes in the membrane lipid composition.

Animals↗
PubMed1983

Modification of microsomal lipid composition and electron transport enzyme activities in isovalerate-supplemented cells of novel Tetrahymena ISO.

Tetrahymena ISO cells, which have an unusually high level of iso odd-numbered fatty acids, were grown medium supplemented with various concentrations of isovalerate. There was a marked increase in the total proportion of iso odd-numbered fatty acids in supplemented whole cells (28.9 leads to 70.3%) and microsomes (37.7 leads to 84%), with a corresponding decrease in normal fatty acids, although no significant alteration of phospholipid composition was observed during 11 hr isovalerate-supplementation. Microsomal palmitoyl-CoA and stearoyl-CoA desaturase activities in isovalerate-supplemented cells decreased by 45.7% and 30.6% during 11 hr, respectively. NADH-cytochrome c reductase and NADH-ferricyanide reductase activities as well as the content of cytochrome b560ms, which is similar to mammalian microsomal cytochrome b5, were reduced in microsomes from 11 hr-supplemented cells, whereas NADPH-cytochrome c reductase activity was constant. It is suggested that the alteration of the cross-sectional area of lipid molecules in the bilayer, which results from the replacement of normal fatty acids with iso- 15:0 and iso- 17:1, would result in the decline of palmitoyl- and stearoyl-CoA desaturation in the isovalerate-supplemented cells, in order to maintain membrane fluidity at a functional level.

Animals↗
PubMed1976

Lipid-mediated protein interaction in membranes.

This study describes the effects ensuing from a non-specific interaction between membrane integral proteins and the surrounding lipids. The results are obtained using an appropriate molecular field theory to describe the ordering of membrane lipids. The modification of the lipid structure near a protein molecule, while most pronounced within the annulus of the first neighbour molecules, extends two or three layers beyond the annulus. The ordering of lipids within the annulus has a modified temperature dependence, and becomes a continuous function of temperature for low lipid/protein ratios. The change in order of lipid molecules surrounding a protein leads to an indirect, lipid-mediated interaction between membrane integral proteins. This interaction depends sensitively on the bulk lipid order. Under favourable circumstances, it gives rise to protein aggregation.

Binding Sites↗
PubMed1980

Age-dependent modifications in membrane lipids: lipid composition, fluidity and palmitoyl-CoA desaturase in Tetrahymena membranes.

The membrane lipid composition of Tetrahymena pyriformis NT-I was observed to change in a manner markedly dependent on the progress of culture age. The pellicular, mitochondrial and microsomal membranes were isolated from cell harvested at various growth phases (I, early exponential; II, mid-exponential; III, late exponential; IV, early stationary; V, late stationary) and their lipid composition was analyzed by thin-layer and gas-liquid chromatography. Although the phospholipid composition varied somewhat among membrane fractions, the most general age-dependent alteration was a considerable decrease in the content of phosphatidylethanolamine accompanied by a small increase in phosphatidylcholine. The 2-aminoethylphosphonolipid, enriched in the surface membrane pellicle, did not undergo a consistent change. As for fatty acid composition the most notable variation occurred in unsaturated fatty acids; a great increase in oleic and linoleic acids and a compensatory decrease in palmitoleic acid. This resulted in an augmented unsaturation of the overall phospholipid fatty acid profile of the aged membranes. The age-associated drastic decline in the palmitoleic acid content in membrane phospholipids could be accounted for by the markedly lowered activity of palmitoyl-CoA desaturase. The microsomes from the early exponential phase cells possess a 4-fold higher activity of the desaturase as compared to that of the late stationary phase microsomes. The decreased desaturase activity associated with the culture age was also reflected in the corresponding decrease in the conversion rate of [14C]palmitate to [14C]palmitoleate in cells labelled in vivo. The ESR spectra of the spin-labeled phospholipids extracted from the pellicular and microsomal membranes have led to the suggestion that these types of membrane would become more fluid with the age of growth.

Animals↗
PubMed1995

Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory.

The technique of fluorescence recovery after photobleaching was used to measure the lateral mobility of membrane integral proteins in reticulocyte plasma membranes which were treated to modify the 'fluid' lipid or immobilized protein fractions, hence increasing the relative prevalence of obstacles to protein lateral motion. This was achieved by either: (1) treating the plasma membranes with phospholipase A2 followed by extraction of the hydrolysis products using fatty-acid-free bovine serum albumin, resulting in a decrease in the membrane 'fluid' lipid portion; or (2) preincubating the plasma membranes with polylysines, resulting in plasma membrane protein aggregation and immobilization. As the prevalence of obstacles to lateral motion increased in plasma membranes through the treatments described above, the mobility of the membrane integral proteins diminished. Experimental results for the dependence of protein mobility on the prevalence of obstacles to lateral motion were compared to theoretical data in order to verify the applicability of the percolation theory to reticulocyte plasma membranes. The influence of a decrease in the 'fluid' lipid and an increase in the immobilized membrane protein fractions upon the hormone-stimulated adenylate cyclase activity has been studied as well. As the 'solid' lipid and immobilized membrane protein fractions decreased, both the hormone-stimulated adenylate cyclase activity and the fraction of beta-adrenergic receptors with high affinity to hormone diminished. It was shown that this correlation can be caused by a decrease in membrane fraction accessible to the movement of the interacting proteins of the adenylate cyclase complex. Hormonal stimulation of adenylate cyclase is discussed in terms of the percolation theory.

Adenylyl Cyclases↗